1. Field of the Invention
The present invention relates to a composition of a stabilized fibroblast growth factor (hereinafter abbreviated as FGF).
2. Prior Art
In 1974, Gospodarowicz found FGF in bovine pituitary gland to be a protein which highly stimulates the proliferation of fibroblast (Nature, vol. 24, page 123, 1974). FGF genes have been cloned, and it has been made possible to produce them in large quantities by genetic recombination technologies. FGF has been hence energetically studied. As a result, it has been revealed that FGF simulates the proliferation of a variety of cells such as capillary endotherial cells, blood vessel smooth muscle cells, cornea endotherial cells, osteoblast and chondrocyte as well as the proliferation of fibroblast.
Like other polypeptides, however, FGF is easily affected by protease, heat, pH, etc., and it has been therefore considered difficult to prepare any practical FGF formulations.
For stabilizing FGF, a method using water-soluble polysaccharide (JP-A-63-152524 as published in corresponding laid-open patent publication EP 0 267 015) and a method using sulfated glucan (JP-A-2-138223 as published in corresponding laid-open patent publication EP 0 345 660) are disclosed. In the method using sulfated glucan, for example, there is disclosed a formulation containing free cyclodextrin sulfate or a formulation containing cyclodextrin sulfate in the form of a highly water-soluble salt such as sodium salt, potassium salt, ammonium salt or trimethylammonium salt. Since, however, the above methods are not yet satisfactory, the present inventors have made a study to improve the stability of FGF to protease, heat, pH, etc.